Dexamethasone inhibits interleukin-1β-induced corneal neovascularization: Role of nuclear factor-κB-activated stromal cells in inflammatory angiogenesis

Shintaro Nakao, Yasuaki Hata, Muneki Miura, Kousuke Noda, Yusuke N. Kimura, Shuhei Kawahara, Takeshi Kita, Toshio Hisatomi, Toru Nakazawa, Yiping Jin, M. Reza Dana, Michihiko Kuwano, Mayumi Ono, Tatsuro Ishibashi, Ali Hafezi-Moghadam

研究成果: Article査読

97 被引用数 (Scopus)

抄録

Dexamethasone, a synthetic corticosteroid, is widely used as a potent anti-inflammatory drug in various diseases including corneal angiogenesis. However, dexamethasone's impact on interleukin (IL)-1β-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-1β-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E2 in the mouse cornea 2 days after IL-1β implantation. IL-1β caused IκB-α phosphorylation in corneal stromal cells but not in infiltrated CD11b+ cells 2 days after IL-1β implantation. In contrast, both cell types were positive for phosphorylated IκB-α 4 days after IL-1β implantation. Dexamethasone significantly inhibited IκB-α phosphorylation 2 and 4 days after IL-1β implantation. Furthermore, dexamethasone inhibited IL-1β-induced expression of vascular endothelial growth factor-A, KC, and prostaglandin E2, and signaling of nuclear factor (NF)-κB in corneal fibroblasts in vitro. A selective NF-κB inhibitor attenuated IL-1β-induced corneal angiogenesis. These findings suggest that NF-κB activation in the corneal stromal cells is an important early event during IL-1β-induced corneal angiogenesis and that dexamethasone inhibits IL-1β-induced angiogenesis partially via blocking NF-κB signaling.

本文言語English
ページ(範囲)1058-1065
ページ数8
ジャーナルAmerican Journal of Pathology
171
3
DOI
出版ステータスPublished - 2007 9月
外部発表はい

ASJC Scopus subject areas

  • 病理学および法医学

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